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2000
Volume 20, Issue 10
  • ISSN: 1574-888X
  • E-ISSN: 2212-3946

Abstract

Introduction

Neural stem cells (NSCs) are vulnerable to oxidative stress, which triggers aging and subsequently leads to a reduced regenerative capacity of the central nervous system (CNS). Due to the challenges in acquiring aged human NSCs and the lack of an oxidative stress-induced aging model specifically designed for human NSCs, research related to the aging mechanisms and the screening of anti-aging drugs has been limited. Here, we aimed to establish an oxidative stress-induced senescence model of NSCs by using D-galactose (D-gal).

Methods

Human embryonic stem cells (hESCs) were differentiated into hESC-NSCs using a type I collagen method. hESC-NSCs were characterized by flow cytometry combined with immunofluorescence. A senescence model of hESC-NSCs was established using D-gal and characterized by CCK-8 assay, neurosphere formation, crystal violet staining, DNA damage assay, SA-β-gal staining, and ROS levels measurement. To further explore the profile of gene expression in the D-gal-induced hESC-NSCs senescence model, transcriptome sequencing was performed and analysed by bioinformatics method, followed by verification using qPCR.

Results

The hESC-derived NSCs senescence model demonstrated reduced proliferation and elevated β-galactosidase activity, accompanied by DNA damage, and increased levels of reactive oxygen species. Furthermore, transcriptome analysis unveiled the potential central role of the MAPK signaling pathway in D-gal-induced senescence, involving key genes, including , , , , and .

Conclusion

We presented an oxidative stress-induced senescence model of hESC-NSCs and identified key pathways and genes related to D-gal-induced senescence. Our study might offer an alternative approach to investigating human NSCs aging and provide valuable data for understanding the underlying mechanisms of oxidative stress-induced aging.

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2026-02-05

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A Human Embryonic Stem Cell-derived Neural Stem Cell Senescence Model Triggered by Oxidative Stress
Curr Stem Cell Res Ther 20, 1036 (2025); https://doi.org/10.2174/011574888X365639250214045110
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  • Article Type:     Research Article
Keyword(s): D-galactose; Human embryonic stem cell; neural stem cell; oxidative stress; senescence; transcriptome sequencing

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